tbuckley/cabot-search huggingface dataset:
Traumatic Life Events and Association With Depression, Anxiety, and Somatization Symptoms in Female Refugees
Authors: James Kenneth Moran, Jenny Jesuthasan, Inga Schalinski, Christine Kurmeyer, Sabine Oertelt-Prigione, Ingar Abels, Ulrich Stangier, Annabelle Starck, Jana Gutermann, Ulrike Zier, Anja Wollny, Kneginja Richter, Antje Krüger, Meryam Schouler-Ocak
Journal: JAMA Network Open (2023)

Importance Different types of traumatic life events have varying impacts on symptoms of depression, anxiety, and somatization. For women from areas of the world experiencing war and humanitarian crises, who have experienced cumulative trauma exposure during war and forced migration, it is not known whether cumulative trauma or particular events have the greatest impact on symptoms. Objective To examine which traumatic life events are associated with depression, anxiety, and somatization symptoms, compared with the cumulative amount, in a sample of female refugees. Design, Setting, and Participants For this cross-sectional study, data were collected in 2016 as a part of The Study on Female Refugees. The current analysis was conducted in 2022 to 2023. This multicenter study covered 5 provinces in Germany. Participants were recruited at reception centers for refugees. Women volunteered to participate and to be interviewed after information seminars at the different centers. Exposure Traumatic life events experienced by refugees from areas of the world experiencing war and humanitarian crises. Main Outcomes and Measures Demographic variables (age, country of origin, religion, education, relationship status, and children), traumatic and adverse life events, and self-reported depression, anxiety, and somatization symptoms were measured. Random forest regressions simultaneously examined the importance of these variables on symptom scores. Follow-up exploratory mediation models tested potential associative pathways between the identified variables of importance. Results For the final sample of 620 refugee women (mean [SD] age, 32.34 [10.35] years), family violence was most associated with depression (mean [SD] variable of importance [VIM], 2.93 [0.09]), anxiety (mean [SD] VIM, 4.15 [0.11]), and somatization (mean [SD] VIM, 3.99 [0.15]), even though it was less common than other traumatic experiences, including war, accidents, hunger, or lack of housing. Other factors, such as childhood sexual abuse, injury, near-death experiences, and lack of access to health care, were also important. Follow-up analyses showed partial mediation effects between these factors in their association with symptoms, supporting the unique importance of family violence in understanding mental health. Conclusions and Relevance The findings of this cross-sectional study of refugee women who experienced multiple severe traumas related to war in their home countries and danger encountered during their migration suggest that family violence was key to their current mental health problems. Culturally sensitive assessment and treatment need to place special emphasis on these family dynamics.
Investigating Associations of Omega-3 Fatty Acids, Lung Function Decline, and Airway Obstruction
Authors: Bonnie K. Patchen, Pallavi Balte, Traci M. Bartz, R. Graham Barr, Myriam Fornage, Mariaelisa Graff, David R. Jacobs, Ravi Kalhan, Rozenn N. Lemaitre, George O’Connor, Bruce Psaty, Jungkyun Seo, Michael Y. Tsai, Alexis C. Wood, Hanfei Xu, Jingwen Zhang, Sina A. Gharib, Ani Manichaikul, Kari North, Lyn M. Steffen, Josée Dupuis, Elizabeth Oelsner, Dana B. Hancock, Patricia A. Cassano
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Inflammation contributes to lung function decline and the development of chronic obstructive pulmonary disease. Omega-3 fatty acids have antiinflammatory properties and may benefit lung health.
Rationale and design of <scp>ENDEAVOR</scp>: A sequential phase 2b–3 randomized clinical trial to evaluate the effect of myeloperoxidase inhibition on symptoms and exercise capacity in heart failure with preserved or mildly reduced ejection fraction
Authors: Lars H. Lund, Carolyn S.P. Lam, Patricia E. Pizzato, Anders Gabrielsen, Erik Michaëlsson, Karin Nelander, Hans Ericsson, Julie Holden, Folke Folkvaljon, Andrea Mattsson, Anna Collén, Malin Aurell, Carl Whatling, Stephan Baldus, Grzegorz Drelich, Assen Goudev, Béla Merkely, Niklas Bergh, Sanjiv J. Shah
Journal: European Journal of Heart Failure (2023)

Aims Mitiperstat (formerly AZD4831) is a novel selective myeloperoxidase inhibitor. Currently, no effective therapies target comorbidity‐induced systemic inflammation, which may be a key mechanism underlying heart failure with preserved or mildly reduced ejection fraction (HFpEF/HFmrEF). Circulating neutrophils secrete myeloperoxidase, causing oxidative stress, microvascular endothelial dysfunction, interstitial fibrosis, cardiomyocyte remodelling and diastolic dysfunction. Mitiperstat may therefore improve function of the heart and other organs, and ameliorate heart failure symptoms and exercise intolerance. ENDEAVOR is a combined, seamless phase 2b–3 study of the efficacy and safety of mitiperstat in patients with HFpEF/HFmrEF. Methods In phase 2b, approximately 660 patients with heart failure and ejection fraction &gt;40% are being randomized 1:1:1 to mitiperstat 2.5 mg, 5 mg or placebo for 48 weeks. Eligible patients have baseline 6‐min walk distance (6MWD) of 30–400 m with a &lt;50 m difference between screening and randomization and Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ‐TSS) ≤90 points at screening and randomization. The dual primary endpoints are change from baseline to week 16 in 6MWD and KCCQ‐TSS. The sample size provides 85% power to detect placebo‐adjusted improvements of 21 m in 6MWD and 6.0 points in KCCQ‐TSS at overall two‐sided alpha of 0.05. Safety is monitored throughout treatment, with a focus on maculopapular rash. In phase 3 of ENDEAVOR, approximately 820 patients will be randomized 1:1 to mitiperstat or placebo. Conclusion ENDEAVOR is the first phase 2b–3 study to evaluate whether myeloperoxidase inhibition can improve symptoms and exercise capacity in patients with HFpEF/HFmrEF.
Errors in Figure 3
Authors: Jian-Feng Huang
Journal: JAMA Oncology (2023)

Connor J. Kinslow, MD; Ann Mercurio, MS, RN; Prashanth Kumar, BA; Ali I. Rae, MD, MPH; Markus D. Siegelin, MD, PhD; Jack Grinband, PhD; Kekoa Taparra, MD, PhD; Pavan S. Upadhyayula, MD; Guy M. McKhann, MD; Michael B. Sisti, MD; Jeffrey N. Bruce, MD; Peter D. Canoll, MD, PhD; Fabio M. Iwamoto, MD; Lisa A. Kachnic, MD; James B. Yu, MD, MHS; Simon K. Cheng, MD, PhD; Tony J. C. Wang, MD
Danicamtiv Increases Myosin Recruitment and Alters Cross-Bridge Cycling in Cardiac Muscle
Authors: Kristina B. Kooiker, Saffie Mohran, Kyrah L. Turner, Weikang Ma, Amy Martinson, Galina Flint, Lin Qi, Chengqian Gao, Yahan Zheng, Timothy S. McMillen, Christian Mandrycky, Max Mahoney-Schaefer, Jeremy C. Freeman, Elijah Gabriela Costales Arenas, An-Yu Tu, Thomas C. Irving, Michael A. Geeves, Bertrand C.W. Tanner, Michael Regnier, Jennifer Davis, Farid Moussavi-Harami
Journal: Circulation Research (2023)

Modulating myosin function is a novel therapeutic approach in patients with cardiomyopathy. Danicamtiv is a novel myosin activator with promising preclinical data that is currently in clinical trials. While it is known that danicamtiv increases force and cardiomyocyte contractility without affecting calcium levels, detailed mechanistic studies regarding its mode of action are lacking.Permeabilized porcine cardiac tissue and myofibrils were used for X-ray diffraction and mechanical measurements. A mouse model of genetic dilated cardiomyopathy was used to evaluate the ability of danicamtiv to correct the contractile deficit.Danicamtiv increased force and calcium sensitivity via increasing the number of myosins in the ON state and slowing cross-bridge turnover. Our detailed analysis showed that inhibition of ADP release results in decreased cross-bridge turnover with cross bridges staying attached longer and prolonging myofibril relaxation. Danicamtiv corrected decreased calcium sensitivity in demembranated tissue, abnormal twitch magnitude and kinetics in intact cardiac tissue, and reduced ejection fraction in the whole organ.As demonstrated by the detailed studies of Danicamtiv, increasing myosin recruitment and altering cross-bridge cycling are 2 mechanisms to increase force and calcium sensitivity in cardiac muscle. Myosin activators such as Danicamtiv can treat the causative hypocontractile phenotype in genetic dilated cardiomyopathy.
Integrated Clinical-Molecular Classification of Colorectal Liver Metastases
Authors: Rohan R. Katipally, Carlos A. Martinez, Siân A. Pugh, John A. Bridgewater, John N. Primrose, Enric Domingo, Timothy S. Maughan, Mark S. Talamonti, Mitchell C. Posner, Ralph R. Weichselbaum, Sean P. Pitroda
Journal: JAMA Oncology (2023)

Personalized treatment approaches for patients with oligometastatic colorectal liver metastases are critically needed. We previously defined 3 biologically distinct molecular subtypes of colorectal liver metastases: (1) canonical, (2) immune, and (3) stromal.
Quantitative proteomics of cerebrospinal fluid from African Americans and Caucasians reveals shared and divergent changes in Alzheimer’s disease
Authors: Erica S. Modeste, Lingyan Ping, Caroline M. Watson, Duc M. Duong, Eric B. Dammer, Erik C. B. Johnson, Blaine R. Roberts, James J. Lah, Allan I. Levey, Nicholas T. Seyfried
Journal: Molecular Neurodegeneration (2023)

Despite being twice as likely to get Alzheimer's disease (AD), African Americans have been grossly underrepresented in AD research. While emerging evidence indicates that African Americans with AD have lower cerebrospinal fluid (CSF) levels of Tau compared to Caucasians, other differences in AD CSF biomarkers have not been fully elucidated. Here, we performed unbiased proteomic profiling of CSF from African Americans and Caucasians with and without AD to identify both common and divergent AD CSF biomarkers.Multiplex tandem mass tag-based mass spectrometry (TMT-MS) quantified 1,840 proteins from 105 control and 98 AD patients of which 100 identified as Caucasian while 103 identified as African American. We used differential protein expression and co-expression approaches to assess how changes in the CSF proteome are related to race and AD. Co-expression network analysis organized the CSF proteome into 14 modules associated with brain cell-types and biological pathways. A targeted mass spectrometry method, selected reaction monitoring (SRM), with heavy labeled internal standards was used to measure a panel of CSF module proteins across a subset of African Americans and Caucasians with or without AD. A receiver operating characteristic (ROC) curve analysis assessed the performance of each protein biomarker in differentiating controls and AD by race.Consistent with previous findings, the increase of Tau levels in AD was greater in Caucasians than in African Americans by both immunoassay and TMT-MS measurements. CSF modules which included 14-3-3 proteins (YWHAZ and YWHAG) demonstrated equivalent disease-related elevations in both African Americans and Caucasians with AD, whereas other modules demonstrated more profound disease changes within race. Modules enriched with proteins involved with glycolysis and neuronal/cytoskeletal proteins, including Tau, were more increased in Caucasians than in African Americans with AD. In contrast, a module enriched with synaptic proteins including VGF, SCG2, and NPTX2 was significantly lower in African Americans than Caucasians with AD. Following SRM and ROC analysis, VGF, SCG2, and NPTX2 were significantly better at classifying African Americans than Caucasians with AD.Our findings provide insight into additional protein biomarkers and pathways reflecting underlying brain pathology that are shared or differ by race.
Errors in the Conflicts of Interest Section, Figure 2, and Affiliations
Journal: JAMA Oncology (2023)

Julien Mazieres, MD, PhD; Paul K. Paik, MD; Marina C. Garassino, MD; Xiuning Le, MD; Hiroshi Sakai, MD; Remi Veillon, MD; Egbert F. Smit, MD, PhD; Alexis B. Cortot, MD, PhD; Jo Raskin, MD; Santiago Viteri, MD; Yi-Long Wu, MD; James C. H. Yang, MD; Myung-Ju Ahn, MD; Rui Ma, MD; Jun Zhao, MD; Aurora O’Brate, PhD; Karin Berghoff, MD, PhD; Rolf Bruns, MSc; Gordon Otto, MD, PhD; Andreas Johne, MD; Enriqueta Felip, MD, PhD; Michael Thomas, MD
Early-set POMC methylation variability is accompanied by increased risk for obesity and is addressable by MC4R agonist treatment
Authors: Lara Lechner, Robert Opitz, Matt J. Silver, Philipp M. Krabusch, Andrew M. Prentice, Martha S. Field, Harald Stachelscheid, Elsa Leitão, Christopher Schröder, Valeria Fernandez Vallone, Bernhard Horsthemke, Karl-Heinz Jöckel, Börge Schmidt, Markus M. Nöthen, Per Hoffmann, Stefan Herms, Patrick W. Kleyn, Matthias Megges, Ulrike Blume-Peytavi, Katja Weiss, Knut Mai, Oliver Blankenstein, Benedikt Obermayer, Susanna Wiegand, Peter Kühnen
Journal: Science Translational Medicine (2023)

Increasing evidence points toward epigenetic variants as a risk factor for developing obesity. We analyzed DNA methylation of the
Targeting the Nerve–Cancer Circuit
Authors: Yi Ye, Tongxin Xie, Moran Amit
Journal: Cancer Research (2023)

Abstract The tumor microenvironment is innervated by sensory, sympathetic, and parasympathetic nerves that actively stimulate cancer growth and dissemination. The cross-talk among the peripheral nerves, cancer cells, and stromal cells is mediated by a diverse set of bioactive ligands and their corresponding receptors. Dissecting the specific neuronal subtypes and molecular signals that drive cancer–nerve interaction holds the hope of developing targeted therapies for cancer. A recent study by Restaino and colleagues demonstrated that regardless of tumor type, origin, or anatomic location, tumors are densely innervated, predominantly by transient receptor potential cation channel subfamily V member 1 positive (TRPV1+) sensory fibers. The intratumoral fibers likely have functional connectivity and contribute to increased electrical activity in the tumor bed. Importantly, the neuropeptide substance P produced by intratumoral fibers stimulates its neurokinin 1 receptor (NK1R) expressed on tumor cells to drive tumor proliferation and migration. The findings raised the intriguing possibility of a generalizable molecular pathway that mediates cancer–nerve interaction that can be targeted to inhibit tumor growth and metastasis across different tumor types.
The Transcriptional and Epigenetic Landscape of Cancer Cell Lineage Plasticity
Authors: Alastair Davies, Amina Zoubeidi, Himisha Beltran, Luke A. Selth
Journal: Cancer Discovery (2023)

Abstract Lineage plasticity, a process whereby cells change their phenotype to take on a different molecular and/or histologic identity, is a key driver of cancer progression and therapy resistance. Although underlying genetic changes within the tumor can enhance lineage plasticity, it is predominantly a dynamic process controlled by transcriptional and epigenetic dysregulation. This review explores the transcriptional and epigenetic regulators of lineage plasticity and their interplay with other features of malignancy, such as dysregulated metabolism, the tumor microenvironment, and immune evasion. We also discuss strategies for the detection and treatment of highly plastic tumors. Significance: Lineage plasticity is a hallmark of cancer and a critical facilitator of other oncogenic features such as metastasis, therapy resistance, dysregulated metabolism, and immune evasion. It is essential that the molecular mechanisms of lineage plasticity are elucidated to enable the development of strategies to effectively target this phenomenon. In this review, we describe key transcriptional and epigenetic regulators of cancer cell plasticity, in the process highlighting therapeutic approaches that may be harnessed for patient benefit.
Evaluating the efficacy of continuous wave carbon dioxide laser therapy in conjunction with biologics for the management of hidradenitis suppurativa
Authors: Jalal Maghfour, Fiatsogbe Dzuali, Nnemaka Ezekwe, Jacobsen Gordon, Iltefat H Hamzavi
Journal: British Journal of Dermatology (2023)

Journal Article Accepted manuscript Evaluating the Efficacy of Continuous Wave Carbon Dioxide Laser Therapy in Conjunction with Biologics for the management of Hidradenitis Suppurativa Get access Jalal Maghfour, Jalal Maghfour Photobiology and Photomedicine Research Unit, Department of Dermatology, Henry Ford Health System, Detroit, MI, USA Search for other works by this author on: Oxford Academic Google Scholar Fiatsogbe Dzuali, Fiatsogbe Dzuali Department of Dermatology, University of California San Francisco, San Francisco, CA, USA Search for other works by this author on: Oxford Academic Google Scholar Nnemaka Ezekwe, Nnemaka Ezekwe Department of Dermatology, University of Colorado Anschutz, Aurora, CO, USA Search for other works by this author on: Oxford Academic Google Scholar Jacobsen Gordon, Jacobsen Gordon Public Health Sciences, Henry Ford Heath, Detroit, MI, USA Search for other works by this author on: Oxford Academic Google Scholar Iltefat H Hamzavi Iltefat H Hamzavi Photobiology and Photomedicine Research Unit, Department of Dermatology, Henry Ford Health System, Detroit, MI, USA Corresponding Author: Iltefat H. Hamzavi MD FAAD, Email:ihamzavi@hamzavi.org Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljad246, https://doi.org/10.1093/bjd/ljad246 Published: 20 July 2023 Article history Received: 25 January 2022 Revision received: 13 July 2023 Editorial decision: 14 July 2023 Accepted: 18 July 2023 Published: 20 July 2023
Multimodal repertoire analysis unveils B cell biology in immune-mediated diseases
Authors: Mineto Ota, Masahiro Nakano, Yasuo Nagafuchi, Satomi Kobayashi, Hiroaki Hatano, Ryochi Yoshida, Yuko Akutsu, Takahiro Itamiya, Nobuhiro Ban, Yumi Tsuchida, Hirofumi Shoda, Kazuhiko Yamamoto, Kazuyoshi Ishigaki, Tomohisa Okamura, Keishi Fujio
Journal: Annals of the Rheumatic Diseases (2023)

Despite the involvement of B cells in the pathogenesis of immune-mediated diseases (IMDs), biological mechanisms underlying their function are scarcely understood. To overcome this gap, here we constructed and investigated a large-scale repertoire catalogue of five B cell subsets of patients with IMDs.We mapped B cell receptor regions from RNA sequencing data of sorted B cell subsets. Our dataset consisted of 595 donors under IMDs and health. We characterised the repertoire features from various aspects, including their association with immune cell transcriptomes and clinical features and their response to belimumab treatment.Heavy-chain complementarity-determining region 3 (CDR-H3) length among naïve B cells was shortened among autoimmune diseases. Strong negative correlation between interferon signature strength and CDR-H3 length was observed in naïve B cells and suggested the role for interferon in premature B cell development. VDJ gene usage was skewed especially in plasmablasts and unswitched-memory B cells of patients with systemic lupus erythematosus (SLE). We developed a scoring system to quantify this skewing, and it positively correlated with peripheral helper T cell transcriptomic signatures and negatively correlated with the amount of somatic hyper mutations in plasmablasts, suggesting the association of extrafollicular pathway. Further, this skewing led to high usage of IGHV4-34 gene with 9G4 idiotypes in unswitched-memory B cells, which showed a prominent positive correlation with disease activity in SLE. Gene usage skewing in unswitched-memory B cells was ameliorated after belimumab treatment.Our multimodal repertoire analysis enabled us the system-level understanding of B cell abnormality in diseases.
The COVID-19 pandemic in Greenland, epidemic features and impact of early strict measures, March 2020 to June 2022
Authors: Paneeraq Noahsen, Louise Lohmann Faber, Silvia Isidor, Jannik Fonager, Morten Rasmussen, Henrik L Hansen
Journal: Eurosurveillance (2023)

BackgroundThe COVID-19 pandemic was of major concern in Greenland. There was a high possibility of rapid transmission in settlements, and an increased risk of morbidity and mortality because of comorbidities in the population and limited access to specialised healthcare in remote areas.AimTo describe the epidemiology of the COVID-19 pandemic in Greenland and evaluate the effects of a strict COVID-19 strategy until risk groups were immunised.MethodsWe studied the epidemiology during March 2020 to June 2022. We describe the non-pharmaceutical interventions (NPIs), PCR-confirmed COVID-19 cases and vaccination coverage with data from the registries of the Greenlandic health authority.ResultsWe found 21,419 confirmed cases per 100,000 inhabitants (54% female, 46% male), 342 per 100,000 were hospitalised and 16 per 100,000 were admitted to the intensive care unit. The COVID-19 mortality rate was 39 per 100,000, all those affected were aged above 65 years. No excess overall mortality was observed. The vaccination coverage by June 2022 was 71.67 and 41% for one, two and three doses, respectively.ConclusionSARS-CoV-2 circulation in Greenland was low, given strict restrictions until all eligible inhabitants had been offered immunisation. The main impact of the pandemic was from May 2021 onwards with increasing numbers of confirmed cases. This occurred after introduction of the vaccine programme, which may have had an influence on the severity of the associated morbidity and mortality experienced. Halting community transmission of SARS-CoV-2 with NPIs until the majority of the population had been immunised was a successful strategy in Greenland.
Association of Successful Percutaneous Revascularization of Chronic Total Occlusions With Quality of Life
Authors: Selcuk Kucukseymen, Mario Iannaccone, James A. Grantham, James Sapontis, Stefan Juricic, Niccolò Ciardetti, Alessio Mattesini, Sinisa Stojkovic, Bradley H. Strauss, Harindra C. Wijeysundera, Gerald S. Werner, Fabrizio D’Ascenzo, Carlo Di Mario
Journal: JAMA Network Open (2023)

Chronic total occlusion percutaneous coronary intervention (CTO-PCI) is not usually offered because of skepticism about long-term clinical benefits.